Increasing demand for food is driving a worldwide trend of agricultural input intensification. However, there is no comprehensive knowledge about the interrelations between potential yield gains and environmental trade-offs that would enable the identification of regions where input-driven intensification could achieve higher yields, yet with minimal environmental impacts. We explore ways of enhancing global yields, while avoiding significant nitrogen (N) emissions (Ne) by exploring a range of N and irrigation management scenarios. The simulated responses of yields and Ne to increased N inputs (Nin) and irrigation show high spatial variations due to differences in current agricultural inputs and agro-climatic conditions. Nitrogen use efficiency (NUE) of yield gains is negatively correlated with incremental Ne due to Nin additions. Avoiding further intensification in regions where high fractions of climatic yield potentials, ≥ 80%, are already achieved is key to maintain good NUE. Depending on the intensification scenarios, relative increases in Ne could be reduced by 0.3-29.6% of the baseline Ne with this intensification strategy as compared to indiscriminate further intensification, at the cost of a loss of yield increases by 0.2-16.7% of the baseline yields. In addition, irrigation water requirements and Nin would dramatically decrease by considering this intensification strategy.